Fig. 5.

Mutations that reduce repression of CLOCK:BMAL1 transactivation by CRY localize to CLOCK PAS-B HI loop. CRY-derepressing mutations arising from a random mutagenesis screen: G332E, H360Y, E367K (18) or directed mutagenesis study, Q361P/W362R (19) are predominantly found on the β-sheet face of CLOCK PAS-B domain and are fully solvent accessible. Residues mutated in these studies are in orange. The locations of the SUMOylation site on BMAL1 PAS-A (K259) (41), the Casein kinase 2 phosphorylation site on BMAL1 (S90) (42), and the phosphorylation site on CLOCK (S42) (43) are also indicated. A double strand DNA is modeled based on the superposition with USF-DNA complex structure (25).